Localization and regulation of IFN-gamma production within the granulomas of murine schistosomiasis in IL-4-deficient and control mice

Eva Rakasz; Arthur M Blum; Ahmed Metwali; David E Elliott; Jie Li; Zuhair K Ballas; Khurram Qadir; Richard  Lynch; Joel V Weinstock

doi:10.4049/jimmunol.160.10.4994

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Localization and regulation of IFN-gamma production within the granulomas of murine schistosomiasis in IL-4-deficient and control mice

Journal article

Peer reviewed

Localization and regulation of IFN-gamma production within the granulomas of murine schistosomiasis in IL-4-deficient and control mice

Eva Rakasz, Arthur M Blum, Ahmed Metwali, David E Elliott, Jie Li, Zuhair K Ballas, Khurram Qadir, Richard Lynch and Joel V Weinstock

The Journal of immunology (1950), Vol.160(10), pp.4994-4999

05/15/1998

DOI: 10.4049/jimmunol.160.10.4994

PMID: 9590248

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Abstract

Schistosome granulomas from normal or IL-4-deficient C57BL/6 mice make little IFN-gamma and show no Th1 polarization. This could signify that these granulomas have few cells capable of IFN-gamma synthesis or that such cells are under tight control. Granulomas can make IL-10 and TGF-beta, which can regulate IFN-gamma synthesis. Using FACS analysis and ELISA, we explored the origin and regulation of IFN-gamma in schistosome granulomas from both IL-4(-/-) and IL-4(+/+) mice. FACS analysis of intracytoplasmic IFN-gamma staining showed that some granuloma Thy1.2+ T cells (CD8+ and CD4+) express IFN-gamma. Granulomas had NK1.1+ cells, but they appeared to produce little or no IFN-gamma. Purified granuloma Thy1.2+ cells made IFN-gamma in vitro, whereas isolated NK1.1+ lymphocytes secreted little even with rIL-12 stimulation. Culture of granuloma cells with blocking anti-IL-10 or anti-TGF-beta mAb or with rIL-12 substantially increased T cell IFN-gamma synthesis, particularly in the IL-4(-/-) animals. Cultured granuloma cells depleted of Thy1.2+ lymphocytes by Ab and C released no IFN-gamma. It is concluded that granuloma IFN-gamma comes from T cells, not NK cells. Also, this T cell-derived IFN-gamma is subject to IL-10 and TGF-beta regulation, which is particularly evident in IL-4(-/-) mice. Thus, the Th2 granuloma of schistosomiasis has large numbers of activated Th1 or Th0 lymphocytes that are under tight restraint.

T-Lymphocytes - physiology

Mice, Inbred C57BL

Transforming Growth Factor beta - physiology

Interleukin-4 - deficiency

Interleukin-10 - physiology

Animals

Female

Granuloma - immunology

Mice

Killer Cells, Natural - metabolism

Interleukin-4 - physiology

Schistosomiasis - immunology

Interferon-gamma - biosynthesis

Details

Title: Subtitle: Localization and regulation of IFN-gamma production within the granulomas of murine schistosomiasis in IL-4-deficient and control mice
Creators: Eva Rakasz - Department of Internal Medicine, University of Iowa, Iowa City 52242, USA
Arthur M Blum
Ahmed Metwali
David E Elliott
Jie Li
Zuhair K Ballas
Khurram Qadir
Richard Lynch
Joel V Weinstock
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.160(10), pp.4994-4999
DOI: 10.4049/jimmunol.160.10.4994
PMID: 9590248
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: DK38327 / NIDDK NIH HHS DK25295 / NIDDK NIH HHS DK02428 / NIDDK NIH HHS
Language: English
Date published: 05/15/1998
Academic Unit: Gastroenterology and Hepatology; Immunology; Internal Medicine
Record Identifier: 9984094706702771

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